Vitamin D intakes'in children do not meet current US Dietary Reference Intake (DRI) recommendations and emerging evidence suggests that a significant number of children, particularly those with darker skin pigmentation, have inadequate levels of serum 25-hydroxyvitamin D [25(OH)D]. In adults, achieving serum 25(OH)D "SO nmol/L has been suggested as a target for sufficiency based on serum parathyroid hormone (PTH) concentrations, calcium absorption and fracture rates. In younger populations, the optimum level of circulating 25(OH)D has not been clearly defined, nor is it known what functional outcome measures are ideal for defining this level. Moreover, it is unknown if these requirements would differ by race. The specific aims of this project are to determine in early pubertal males (aged 10 to 13 years;n=160) and females (aged 9 to 12 years;n=160) living in northern and southern regions of the US: 1) whether, and to what degree, oral vitamin D supplementation alters intermediate endpoints of vitamin D and bone metabolism [i.e., serum 25(OH)D, PTH and 1,25(OHhD, fractional calcium absorption, and biochemical markers of bone turnover];2) if race modifies the responses of these intermediate endpoints of vitamin D and bone metabolism to vitamin D supplementation;and 3) to elucidate the relationships between 25(OH}D concentration and each of the variables serum PTH, 1,25(OH)2D and fractional calcium absorption, with particular interest in determining whether there is a point of "diminishing returns" at which increases in 25(OH)D are associated with increasingly small changes in the other variables. Vitamin D3 supplement doses of 0 IU (placebo;n=64), 400 IU [set as the current American Academy of Pediatrics recommendation (n=64)], 1,000 IU (n=64), 2,000 IU (n=64), and 4,000 IU (n=64) will be used in this 12-week (wintertime), double blind, randomized, placebo-controlled trial. To assess if racial differences exist in the biochemical responses to vitamin D supplementation, the groups will be stratified by race (white and black). Subjective measures of sun exposure will also be obtained to estimate the cutaneous synthesis of vitamin D. It is hypothesized that following 12 weeks of vitamin D supplementation, a dose-response relationship will be observed between vitamin D supplementation and equilibrium mean values of the following response variables: serum 25(OH}D, PTH and 1 ,25(OHhD, fractional calcium absorption, and biochemical markers of bone turnover. Our second hypothesis is that race will modify the responses of these intermediate endpoints of vitamin D and bone metabolism to increasing doses of oral vitamin D. This proposed dual-site and multidisciplinary project will address key research priorities identified in the 2006 DRI Research Synthesis Workshop and the 2007 Agency for Healthcare Research and Quality Evidence Report and will advance our understanding of the vitamin D needs of growing children based on serum 25(OH)D and intermediate endpoints of skeietai heaith. The findings from this study have important pubiic health implications with respect to vitamin D intake recommendations aimed at improving the health of US children.